Considerable advances have been made in recent years in screening for genetic traits, and DNA sequence data from the Human Genome Project, combined with advances in testing technology is expected to make genetic DNA-based testing increasingly common. See, e.g., Chee et al., 1996, Science 274:610-614. One area in which genetic testing is widely used is for prenatal screening of genetic traits. Most commonly, this analysis involves obtaining fetal cells by chorionic villus sampling (CVS) or amniocentesis, culturing the cells to metaphase, and generating a karyotype. However, both CVS and amniocentesis are invasive procedures which carry a risk of inducing miscarriage, and tend to be applied to mothers whose risk of bearing a chromosomally abnormal fetus exceeds that of the risk of procedure-induced miscarriage. In general, the procedures are offered to women over 35 years-old.
An alternative approach is analysis of fetal cells that cross the placenta and enter maternal circulation. Fetal blood cells are reported to enter the maternal circulation as early as 7 weeks post-conception and are found at a frequency of about 5 cells/ml of maternal blood from the first trimester onwards. Genetic analysis of these fetal cells could provide a safe and accurate way of screening for common aneuploidies (in particular Down syndrome) and other genetic traits. See, e.g., Chueh and Golbus, 1990, Seminar Prenat. 14:471; Zheng et al., 1993, Med. Genet. 30:1051-56; and Ganshirt-Ahlert et al., 1993, Am. J. Reprod. Immunol. 30:194-201. Thus, a need exists for new methods for isolating and analyzing DNA from fetal cells in maternal circulation.
There is also a need for new methods of isolating DNA from cells, other than fetal cells, that are present at low frequency in a population of cells. For example, methods for isolation and analysis of rare malignant cells present in a population consisting primarily of non-malignant cells would aid in diagnosis and treatment of disease (e.g., screening for a genetic lesion giving rise to the malignant state). Thus, a need also exists for improved methods for DNA analysis of various types of rare cells in a population.